Recent studies have documented hyperglycemia, insulin resistance, and glucose intolerance in a seemingly increasing proportion of patients with HIV infection. Other studies have described a variety of syndromes of fat accumulation and fat loss, including abdominal obesity. Although initially attributed specifically to protease inhibitors (PI), these abnormalities also have been observed in antiretroviral-experienced but PI-naive patients. Hyperinsulinemia and abdominal obesity are strong independent risk factors for coronary artery disease. In noninfected patients, metformin and thiazolidinediones have been shown to reduce insulin resistance by different mechanisms and also to reduce visceral adiposity. This study investigates the use of metformin and rosiglitazone, a member of the thiazolidinedione class, in HIV-infected patients with hyperinsulinemia and central fat accumulation.